Bottom Line:
Gli1+ cells are typical MSCs in vitro.Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population.Twist1(+/-) mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells.

ABSTRACTBone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial-bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the main MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population. Twist1(+/-) mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair.

Mentions:
We hypothesized that Gli1+ cells are MSCs for craniofacial bones, as they are for the incisor mesenchyme26. First, we investigated the expression of Gli1 in mouse calvarial bones. At postnatal day 0 (P0), Gli1+ cells are detectable throughout the entire periosteum, dura and suture mesenchyme, but not in the fontanelles or osteocytes (Figure 1a, g). A similar distribution pattern was detectable at P7 and P14 (Figure 1b-c, h-i). Between P21 and 1 month postnatally, Gli1+ cells are gradually restricted to the suture region (Figure 1d-e). At one month of age, Gli1+ cells are only detectable within the suture mesenchyme, mostly in the mid-suture region, but are absent from the periosteum, dura and osteocytes (Figure 1j-l). Such a suture-specific pattern was also detectable in mice at three months of age and older (Figure 1f).

Mentions:
We hypothesized that Gli1+ cells are MSCs for craniofacial bones, as they are for the incisor mesenchyme26. First, we investigated the expression of Gli1 in mouse calvarial bones. At postnatal day 0 (P0), Gli1+ cells are detectable throughout the entire periosteum, dura and suture mesenchyme, but not in the fontanelles or osteocytes (Figure 1a, g). A similar distribution pattern was detectable at P7 and P14 (Figure 1b-c, h-i). Between P21 and 1 month postnatally, Gli1+ cells are gradually restricted to the suture region (Figure 1d-e). At one month of age, Gli1+ cells are only detectable within the suture mesenchyme, mostly in the mid-suture region, but are absent from the periosteum, dura and osteocytes (Figure 1j-l). Such a suture-specific pattern was also detectable in mice at three months of age and older (Figure 1f).

Bottom Line:
Gli1+ cells are typical MSCs in vitro.Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population.Twist1(+/-) mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells.

ABSTRACTBone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial-bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the main MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population. Twist1(+/-) mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair.